{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE307nnn/GSE307554/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Other"],"species":["Mus musculus"],"gds_type":["Other"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE307554"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Targetable treatment resistance in thyroid cancer with clonal hematopoiesis [EMseq_Macs_5mC_PSV815_Project14046DI]","description":"Anaplastic thyroid cancer (ATC) is a clinically aggressive malignancy with a dismal prognosis. Combined BRAF/MEK inhibition offers significant therapeutic benefit in patients with BRAFV600E-mutant ATCs. However, relapses are common and overall survival remains poor. Compared with differentiated thyroid cancer, a hallmark of ATCs is significant infiltration with myeloid cells, particularly macrophages. ATCs are most common in the aging population, which also has an increased incidence of TET2-mutant clonal hematopoiesis (CH). CH-mutant macrophages have been shown to accelerate CH-associated pathophysiology including atherosclerosis. However, the clinical and mechanistic contribution of CH-mutant clones to solid tumour biology, prognosis and therapeutic response has not been elucidated. Here we show that TET2-mutant CH is enriched in the tumour microenvironment of patients with solid tumours and associated with adverse prognosis in ATC patients. We find that Tet2-mutant macrophages selectively infiltrate mouse BrafV600E-mutant ATC and that their overexpression of Tgfβ-family ligands mediates resistance to BRAF/MEK inhibition. Importantly, inhibition of Tgfβ signalling restores sensitivity to MAPK pathway inhibition, opening a path for synergistic strategies to improve outcomes of patients with ATCs and concurrent CH.","dates":{"publication":"2026/09/28"},"accession":"GSE307554","cross_references":{"GSM":["GSM9226670","GSM9226671","GSM9226672","GSM9226673","GSM9226674","GSM9226675"],"GPL":["24247"],"GSE":["307554"],"taxon":["Mus musculus"]}}